Mechanical tumor microenvironment and transduction: cytoskeleton mediates cancer cell invasion and metastasis

Metastasis is a complicated, multistep process that is responsible for over 90% of cancer-related death. Metastatic disease or the movement of cancer cells from one site to another requires dramatic remodeling of the cytoskeleton. The regulation of cancer cell migration is determined not only by biochemical factors in the microenvironment but also by the biomechanical contextual information provided by the extracellular matrix (ECM). The responses of the cytoskeleton to chemical signals are well characterized and understood. However, the mechanisms of response to mechanical signals in the form of externally applied force and forces generated by the ECM are still poorly understood. Furthermore, understanding the way cellular mechanosensors interact with the physical properties of the microenvironment and transmit the signals to activate the cytoskeletal movements may help identify an effective strategy for the treatment of cancer. Here, we will discuss the role of tumor microenvironment during cancer metastasis and how physical forces remodel the cytoskeleton through mechanosensing and transduction.